Major Depression is a disorder characterized by both affective and neurovegetative symptoms that occurs throughout the lifespan. In general, it is associated with subjective distress, excess disability, and increased mortality. Though the frail, institutional elderly are at high risk for depression, they have been neglected in both clinical practice and research. This study will investigate the significance of affective and neurovegetative symptoms and will evaluate the risks versus the benefits of the use of tricyclic antidepressants in frail elderly patients living within an institutional setting. Patients with depression and coexisting chronical medical or neurological disease will be included. The research will consist of a double-blind, placebo-controlled study of the safety and efficacy of the antidepressant nortripyline in patients with symptoms consistent with a diagnosis of DSMIII Major Depression. Nortriptyline is chosen for investigation because it is the most understood and best investigated of the tricyclic antidepressants. Of those agents that are well tolerated in the elderly, it is the only one for which one can specify, in terms of blood levels, what constitutes adequate treatment. One goal of these studies is validation of the diagnosis of Major Depression among the frail aged, a group where demoralization and the somatic symptoms of chronic illness can make the evaluation of depressive symptoms difficult. Another goal is to provide data that will allow optimal use of antidepressant medication in the institutional elderly and other similar patients in the community. the focus of this research will be on identifying those patient characteristics that predict both therapeutic response and adverse reactioos during drug treatment. Response will be monitored with selfratings, psychiatric interviews, and behavioral assessments. Evaluation of adverse reactions will include monitoring for cardiovascular and cognitive toxicity of the medication, and systematic assessment of subjective side effects. Plasma levels of nortriptyteins will be measured. The study will evaluate the value of detailed monitoring of the response to a test dose of nortriptyline for predicting dosing requirements and for identifying patients at high risk for serious adverse drug effects.